4.3 Article

Anti-rituximab antibodies affect pharmacokinetics and pharmacodynamics of rituximab in children with immune-mediated diseases

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CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
卷 40, 期 1, 页码 183-190

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CLINICAL & EXPER RHEUMATOLOGY

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rituximab; pharmacokinetics; pharmacodynamics

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  1. Emma Children's Hospital Foundation (Stichting Steun Emma)

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This study investigates the impact of anti-drug antibodies (ADA) on the pharmacokinetics and pharmacodynamics of rituximab (RTX) in children, and finds that ADA affects the concentration and efficacy of RTX, especially in patients with systemic lupus erythematosus (SLE).
Objective Rituximab (RTX) is a chimeric monoclonal CD20-antibody. Lack of efficacy has been suggested to be related to the presence of anti-drug antibodies (ADA). The aims of this study were to determine if ADA impact the pharmacokinetics (PK) and pharmacodynamics (PD) of RTX in children, whether the formation of ADA differs between various immune-mediated diseases and if it is related to the occurrence of infusion-related reactions (IRR). Methods All children <18 years who had received RTX treatment in our center between December 2006 and February 2020 with known ADA/RTX-levels, were retrospectively included. The presence of ADA was defined as a titre >8 AU/ml. Results Of twenty-six children treated with RTX for various immune-mediated diseases, six patients were ADA-positive (23.1%). In all ADA-positive patients, RTX concentrations were undetectable in contrast to ADA-negative patients (median RTX concentration 3.1 mu g/ml; IQR 0.57-12.0; p<0.001). Failure of B cell depletion was found in 5/6 ADA-positive and 1/19 ADA-negative patients (p=0.003). In SLE-patients, 50.0% (n=4/8) had developed RTX-ADA. Severe anaphylaxis (n=3) occurred only in the ADA-positive group. Conclusion In our cohort of paediatric patients, undetectable RTX concentrations were found in ADA-positive patients, indicative that these ADA have a PK impact. RTX-ADA also seem to affect the PD, as in the majority of these patients, B cell depletion failed. ADA were most present in SLE-patients and anaphylactic reactions occurred only in ADA-positive patients. With this knowledge, a change of drug might be considered in the presence of RTX-ADA.

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